The three-dimensional (3D) organization of the nucleus has been shown to be important in genomic stability [Zink D, Fischer A H, Nickerson J A: Nuclear structure in cancer cells. (2004)Nat Rev Cancer, 4:677-687], and any change(s) in this organization potentially cause genomic instability [Mai S, Garini Y: Oncogenic remodeling of the three-dimensional organization of the interphase nucleus: c-Myc induces telomeric aggregates whose formation precedes chromosomal rearrangements. (2005) Cell Cycle, 4:1327-1331. Epub Oct. 5, 2005; Mai S and Garini Y: The significance of telomeric aggregates in the interphase nuclei of tumor cells. (2006) J Cell Biochem, 97:904-915. Review].
At present, there is inexact knowledge of about the 3D organization of centromeres in normal, immortalized and tumor cells. However, this knowledge is of fundamental importance to the structural and functional organization of the normal nucleus and to the puzzle of genomic instability in tumor cells.
Previous studies reported on a dynamic organization of centromeres during the cell cycle [Solovei I, Schermelleh L, During K, Engelhardt A, Stein S, Cremer C, Cremer T: Differences in centromere positioning of cycling and postmitotic human cell types. (2004) Chromosoma, 112:410-423. Epub Jun. 9, 2004], during folliculogenesis of mouse oocytes [Garagna S, Merico V, Sebastiano V, Monti M, Orlandini G, Gatti R, Scandroglio R, Redi C A, Zuccotti M: Three-dimensional localization and dynamics of centromeres in mouse oocytes during folliculogenesis. (2004) J Mol Histol, 35:631-638] and during differentiation of human embryonic stem cells [Wiblin A E, Cui W, Clark A J, Bickmore W A: Distinctive nuclear organisation of centromeres and regions involved in pluripotency in human embryonic stem cells. (2005) J Cell Sci, 118(Pt 17):3861-3868. Epub Aug. 16, 2005]. However, centromeric changes during cellular immortalization and transformation have not been previously examined.